Heparin failure and COVID-19: Should we explore other anticoagulants? An observational report regarding in-vitro recovery of anticoagulant action in COVID-19 patients in intensive care

Thomas, Will; White, Danielle; Cox‐Morton, Sally; MacDonald, Stephen; Besser, Martin

doi:10.1016/j.thromres.2020.08.010

Cited by 10 publications

(7 citation statements)

References 13 publications

(14 reference statements)

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“…We found that an excess of heparin slightly increased the proteolytic activity of CatG [ 33 ]. In particular, further investigations are warranted with the significant number of COVID-19 patients who did not benefit from heparin treatment [ 34 , 35 ].…”

Section: Resultsmentioning

confidence: 99%

Camostat Does Not Inhibit the Proteolytic Activity of Neutrophil Serine Proteases

et al. 2022

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Coronavirus disease 2019 (COVID-19) can lead to multi-organ failure influenced by comorbidities and age. Binding of the severe acute respiratory syndrome coronavirus 2 spike protein (SARS-CoV-2 S protein) to angiotensin-converting enzyme 2 (ACE2), along with proteolytic digestion of the S protein by furin and transmembrane protease serine subtype 2 (TMPRSS2), provokes internalization of SARS-CoV-2 into the host cell. Productive infection occurs through viral replication in the cytosol and cell-to-cell transmission. The catalytic activity of TMPRSS2 can be blocked by the trypsin-like serine protease inhibitor camostat, which impairs infection by SARS-CoV-2. At the site of infection, immune cells, such as neutrophils, infiltrate and become activated, releasing neutrophil serine proteases (NSPs), including cathepsin G (CatG), neutrophil elastase (NE), and proteinase 3 (PR3), which promote the mounting of a robust immune response. However, NSPs might be involved in infection and the severe outcome of COVID-19 since the uncontrolled proteolytic activity is responsible for many complications, including autoimmunity, chronic inflammatory disorders, cardiovascular diseases, and thrombosis. Here, we demonstrate that camostat does not inhibit the catalytic activity of CatG, NE, and PR3, indicating the need for additional selective serine protease inhibitors to reduce the risk of developing severe COVID-19.

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Section: Resultsmentioning

confidence: 99%

Camostat Does Not Inhibit the Proteolytic Activity of Neutrophil Serine Proteases

et al. 2022

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“…In this patient, anticoagulation was switched to argatroban, a direct oral anticoagulant (DOAC), and there is evidence that adequate anticoagulation has been achieved with argatroban [5,14]. It has also been speculated that DOAC therapy may yield a theoretical advantage since its mechanism is free from antithrombin [15]. Limited studies have looked at the efficacy of other anticoagulative agents used in hospitalized COVID-19 patients and concluded that apixaban has similar efficacy to enoxaparin in decreasing mortality in those with moderate or severe illness from COVID-19 [16].…”

Section: Discussionmentioning

confidence: 99%

A Case of COVID-19 Related Coagulopathy Complications and Heparin Resistance

Chowdhry¹,

Moshman²,

Carroll³

2021

Cureus

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Mechanisms of COVID-19 coagulopathy have been speculated and are not definitively understood; the current speculation is that there is elaborate crosstalk between the inflammatory and hemostatic systems which contributes to the overall increased thrombotic risk in the setting of COVID-19 resulting in a hypercoagulable state. A few documented reports regarding cases of apparent heparin resistance in patients with COVID-19 with complications of thromboembolic events occurring in the setting of heparin anticoagulation have been described. This phenomenon of heparin resistance has been observed in patients with active, severe COVID-19 infection. However, we describe a unique case of a patient who had recovered from a recent, mild COVID-19 infection that did not require hospitalization and presented with acute limb ischemia and demonstrated heparin resistance. The patient was managed by specialists in vascular surgery, intensivists, cardiologists, hematology, and physical medicine and rehabilitation (PMR). We present the case of a patient who had successfully recovered from COVID-19 yet demonstrated post-COVID-19 complications related to coagulopathy and heparin resistance.

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“…Another study by the same group showed reduced in vitro recovery of anti‐Xa levels with LMWH compared with the direct oral anticoagulants rivaroxaban and apixaban in ICU patients. Again, no correlation with AT deficiency was observed 28 . A comparison of anti‐FXa activity in patients with COVID‐19 administered prophylactic LMWHs identified significantly lower mean anti‐FXa levels in ICU patients compared with ward‐level patients, with 95% of ICU patients failing to achieve an anti‐FXa level of 0.2–0.4 IU/ml versus 27% of ward patients 29 .…”

Section: Heparin Resistance In Covid‐19: Clinical Aspectsmentioning

confidence: 95%

Heparin – Messias or Verschlimmbesserung?

Swan

Carrier

Lisman

et al. 2021

Journal of Thrombosis and Haemostasis

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A heightened risk of thrombosis noted early on with the severe acute respiratory syndrome coronavirus 2 infection led to the widespread use of heparin anticoagulation in the coronavirus disease 2019 (COVID‐19) pandemic. However, reports soon started appearing in the literature where an apparent failure of heparin to prevent thrombotic events was observed in hospitalized patients with this viral infection. In this review, we explore the likely mechanisms for heparin failure with particular relevance to COVID‐19. We also explore the role of anti‐Xa assays and global hemostatic tests in this context. The current controversy of dosing heparin in this disease is detailed with some possible mechanistic reasons for anticoagulant failure. We hope that lessons learnt from the use of heparin in COVID‐19 could assist us in the appropriate use of this anticoagulant in the future.

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Heparin failure and COVID-19: Should we explore other anticoagulants? An observational report regarding in-vitro recovery of anticoagulant action in COVID-19 patients in intensive care

Cited by 10 publications

References 13 publications

Camostat Does Not Inhibit the Proteolytic Activity of Neutrophil Serine Proteases

Camostat Does Not Inhibit the Proteolytic Activity of Neutrophil Serine Proteases

A Case of COVID-19 Related Coagulopathy Complications and Heparin Resistance

Heparin – Messias or Verschlimmbesserung?

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